EFFECT OF DIAZEPAM AND OTHER CENTRAL NERVOUS SYSTEM DEPRESSANTS ON SPINAL REFLEXES IN CATS: A STUDY OF SITE OF ACTION

¹ Departments of Anesthesiology and Pharmacology, College of Physicians and Surgeons, Columbia University, and the Anesthesiology Service, Presbyterian Hospital, New York, New York

In midcollicular decenebnate cats, polysynaptic (ipsilateral and contralateral extensor) reflexes elicited by sciatic nerve stimulation were depressed to 50% or less of the control by diazepam (0.05-02 mg/kg), chlordiazepoxide (10-30 mg/kg), meprobamate (20-40 mg/kg), mephenesin (10-50 mg/kg) and pentobarbital (4 mg/kg), administered intravenously. Blockade of these reflexes by this group of drugs was immediate and lasted for a varying period up to 4 hr. Inhalation of cyclopropane (2.5%, inspired) or nitrous oxide (50%, inspired) also reduced these reflexes to a similar degree. If the spinal cord was transected at the cervical level during the period of drug-induced depression, the ipsilateral reflexes usually became exaggerated, and the contralateral reflexes returned but were usually less pronounced than those in the predrug control period. After spinal tnansection, both of these reflexes were relatively resistant to depression by these drugs, especially diazepam, which was effective only with a total dose of 3 to 10 mg/kg. In both decenebrate and spinal cats, diazepam, chlordiazepoxide, meprobamate and mephenesin did not significantly alter the monosynaptic reflexes (knee jerks). Pentobarbital, cyclopropane and nitrous oxide reduced the monosynaptic reflexes, but not as much as they reduced the polysynaptic responses. These findings suggest that central depressants, such as diazepam, chlondiazepoxide meprobamate and mephenesin, and some anesthetics, such as cyclopropane and nitrous oxide, act upon supraspinal structures, most likely the reticular facilitatony system, in blocking the spinal polysynaptic reflexes. The spinal cord itself appears to be relatively resistant to depression by these agents.

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